PXD061693

PXD061693 is an original dataset announced via ProteomeXchange.

Title	Cell-Surface RNA Forms Ternary Complex with RNA-Binding Protein and Heparan Sulfate to Recruit Immune Receptors Complex with RNA-Binding Protein and Heparan Sulfate to Recruit Immune Receptor
Description	Recent discoveries have shown the presence of RNA molecules on the cell surface, defying the traditional view that RNA only functions intracellularly. However, it is not well understood how cell-surface RNA (csRNA) is stably present on the plasma membrane and what functions it performs. We answer the pressing questions in the emerging field by taking integrated omic-wide approaches and multiple orthogonal validatory methods. Firstly, we exploited the RNA-sensing ability of TLR7 as a specific recombinant probe to detect csRNA. Coupling it with a genome-wide CRISPR-Cas9- knockout screening, we identified heparan sulfate (HS) as a crucial factor for RNA presentation on cells. Using the TLR7 probe, cell surface proximity labelling revealed that these HS-associated csRNAs (hepRNAs) are in vicinity with a plethora of RNA-binding proteins. The compelling observation led us to a molecular model where HS, RNA and RBP form ternary complexes at cell surface. A novel photochemical RNA-protein crosslinking technology termed SCOOPS were then established to validate the termolecular model in a TLR7-orthogonal manner. Moreover, enabled by SCOOPS, we unveiled identities of hepRNA using next-generation sequencing, and identified traits in RNA primary structures that facilitate HS association. We further show that hepRNA binds to killer cell immunoglobulin-like receptor 2DL5 (KIR2DL5), recruiting the protein to cell surface and potentially enhancing receptor-ligand interactions. Our findings provide a foundation for exploring how cell-surface ribonucleoproteins contribute to immune modulation.
HostingRepository	PRIDE
AnnounceDate	2025-11-11
AnnouncementXML	Submission_2025-11-11_00:52:53.177.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dick Zijlmans
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-11 04:23:35	ID requested
⏵ 1	2025-11-11 00:52:53	announced

Dataset with its publication pending

submitter keyword: heparane sulfate, Immunity,RNA, cell surface, RNA-binding proteins

Zeshi Li
contact affiliation	Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
contact email	z.li@uu.nl
lab head
Dick Zijlmans
contact affiliation	Radboud Universiteit Nijmegen
contact email	d.zijlmans@science.ru.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD061693

PRIDE project URI

• PRIDE
  1. PXD061693
     1. Label: PRIDE project
     2. Name: Cell-Surface RNA Forms Ternary Complex with RNA-Binding Protein and Heparan Sulfate to Recruit Immune Receptors Complex with RNA-Binding Protein and Heparan Sulfate to Recruit Immune Receptor